MORPHOLOGICAL CHANGES IN THE ENDOCRINE PANCREAS IN PREGNANT RATS WITH EXPERIMENTAL DIABETES

1979 ◽  
Vol 80 (2) ◽  
pp. 175-179 ◽  
Author(s):  
F. A. VAN ASSCHE ◽  
L. AERTS ◽  
W. GEPTS

This present study has demonstrated that during normal pregnancy in the rat the number of β-cells is increased (hyperplasia) and the volume of the individual β-cells is increased (hypertrophy). During experimental diabetes, however, the endocrine pancreas has an impaired capacity to compensate during pregnancy. In the experimental diabetic pregnant rat the β-cells cannot replicate due to the unfavourable metabolic environment. This could reflect the complications caused by diabetes during human pregnancy.

1977 ◽  
Vol 73 (2) ◽  
pp. 339-NP ◽  
Author(s):  
L. AERTS ◽  
F. A. VAN ASSCHE

SUMMARY The endocrine pancreas of foetuses and newborn rats of experimental diabetic mothers showed morphological and ultrastructural changes. Islet hypertrophy and β cell hyperplasia were constantly present, but the β cells of foetuses of severely diabetic mothers were degranulated. The ultrastructural changes indicated hyperfunction in the β cells of foetuses of experimental diabetic mothers. The morphological changes mentioned were similar to those seen in human diabetic pregnancy.


1972 ◽  
Vol 53 (1) ◽  
pp. 31-35 ◽  
Author(s):  
K. BROWN-GRANT ◽  
C. S. CORKER ◽  
F. NAFTOLIN

SUMMARY Plasma luteinizing hormone (LH) concentrations were already lower on Day 2 of pregnancy than at the same time after the preceding ovulation in the non-pregnant rat, and fell progressively up to Day 16 of pregnancy. No evidence was obtained of any increase at the time when the ovulatory surge of LH would have occurred if the animal had not become pregnant. Pituitary LH concentration was lower in mated rats on the morning of Day 0 of pregnancy than in unmated controls on the morning of the day of oestrus. Subsequently it increased slowly to reach a level higher than at any stage of the oestrous cycle by Day 8 of pregnancy and remained high until at least Day 16 of pregnancy. Peripheral plasma oestradiol concentration increased late on Day 2 of pregnancy and was still raised on Day 4 but was never more than about one fourth of the peak concentration seen on the morning of prooestrus during the oestrous cycle. There were similar changes in plasma LH and oestradiol concentrations in the 48 h after a single injection of 2·5mg progesterone on the morning of the day of dioestrus, a procedure that delays ovulation by 1 or 2 days. Administration of a synthetic progestational compound (medroxyprogesterone acetate) to pregnant rats delayed blastocyst implantation and the delay was associated with a marked decrease in peripheral plasma LH to levels below those of normal pregnancy.


1975 ◽  
Vol 152 (3) ◽  
pp. 433-443 ◽  
Author(s):  
R G Rodway ◽  
N J Kuhn

Treatment of pregnant rats with human chorionic gonadotrophin, luteotrophin (luteinizing hormone), luteotrophin-releasing hormone, prostaglandin F2α, aminoglutethimide, or by foetoplacental removal or hysterectomy achieved a common multiple-response pattern, namely increased activity of luteal 20α-hydroxy steroid dehydrogenase with decreased activity of delta5-3β-hydroxy steriod dehydrogenase and release of delta4-3-oxo steroids in vitro. 2. Similar effects of foetoplacental removal are noted in pregnant mice. 3. Gonadotrophin induced lower activities of 20α-hydroxy steroid dehydrogenase, except at the very end of pregnancy, and partly inhibited the induction caused by foetoplacental removal. 4. The results suggest that existence of a placental factor that restrains these changes until the end of normal pregnancy, which is produced in amounts proportional to the number of placentae and is conveyed to the ovary via the blood. 5. This factor was not replaced by prolactin. 6. It is argued that neither placental lactogen nor pituitary luteotrophin participate in the induction of 20α-hydroxy steroid dehydrogenase at late pregnancy in the rat. 7. Aminoglutethimide induced 20α-hydroxy steroid dehydrogenase only in late pregnancy. This was partly reversed by progesterone, wholly reversed by progesterone plus oestrogen, and did not involve the pituitary.


1981 ◽  
Vol 90 (2) ◽  
pp. 179-191 ◽  
Author(s):  
S. HENDRICKS ◽  
C. A. BLAKE

The effects of varying amounts of copulatory stimulation on patterns of plasma concentrations of prolactin and progesterone were evaluated in 3- and 12-month-old female rats. The 12-month-old group included rats which still exhibited oestrous cycles and rats in persistent vaginal oestrus (PVO). The extent of copulatory stimulation was defined by the number of intromissions received during mating: ≤5,15 or > 50. Blood samples were drawn over the 8 days after mating through a cannula inserted into the right external jugular vein. Plasma from the samples was assayed for prolactin and progesterone. In aged but still cyclic rats, pregnancy rates were positively correlated with the number of intromissions received during mating. Only one rat in PVO became pregnant. All animals which became pregnant and rats in PVO which, after mating, exhibited a disruption of the pattern of PVO, showed the nocturnal surge of plasma prolactin characteristic of pregnant and pseudopregnant rats. While these surges persisted until day 8 after mating in pregnant animals, they were absent by this time in the rats in PVO. Prolactin surges were present in some but not all of the aged rats which did not become pregnant. Progesterone concentrations were raised in all pregnant animals except the one pregnant rat in PVO and, while not related to the number of intromissions, concentrations were higher 8 days after mating in young compared with those in aged pregnant rats. Plasma progesterone was low in rats in PVO regardless of disruption of the pattern of PVO. We have concluded that the failure of limited copulatory stimulation to induce pregnancy in older rats results, at least in part, from its failure to initiate nocturnal prolactin surges. Nevertheless, our data suggest that matings which are not experimentally limited should provide ample stimulation to establish such surges. Although reduced plasma concentrations of prolactin and progesterone at pro-oestrus and reduced plasma progesterone through part of gestation may contribute to decreasing fertility in aged rats, other unidentified factors appear to be involved in mediating the capacity of extensive copulatory stimulation to induce pregnancy in these animals.


1986 ◽  
Vol 60 (5) ◽  
pp. 1704-1709 ◽  
Author(s):  
B. W. Craig ◽  
J. Treadway

The purpose of this investigation was to examine the relationship between an exercise program and fetal development to determine whether training could influence insulin sensitivity in the pregnant rat. Prior to impregnation one group of animals was exercise trained on a Quinton shock-stimulus rodent treadmill. The exercised group was trained to run 5 days/wk, for 2.0 h/day at 31 m/min up an 8 degree incline for 8 wk before mating. Following mating the training intensity was reduced to 27 m/min up a 5 degree incline, and the exercise period decreased to 1 h/day. On day 19 of gestation, 24 h postexercise for the trained mothers, the animals were killed in the fed state and the parametrial fat pads were removed. The parametrial depot of the trained mother was smaller than the sedentary control dam. This was due to a change in cell size and did not involve alterations in cell number. Isolated adipocytes of the parametrial fat pads were used to measure the rates of 2-deoxy-D-[3H]glucose uptake and D-[1–14C]glucose oxidation to 14CO2. The results indicated that the adipocytes from the dam trained prior to and during pregnancy were significantly (P less than 0.05) more responsive to insulin than those of animals remaining sedentary during the same period. At the maximal insulin concentration tested, the fat cells from trained mothers were able to take up and metabolize approximately twice as much glucose as the sedentary control dams. However, the increase in insulin responsiveness induced by the training program did not match the changes observed in trained nonpregnant rats of prior investigations.


1984 ◽  
Vol 102 (3) ◽  
pp. 357-363 ◽  
Author(s):  
B. J. Waddell ◽  
N. W. Bruce

ABSTRACT Both production rate and metabolic clearance rate (MCR) of progesterone may vary rapidly and so effect short-term changes in blood concentration of the hormone. Here, a constant infusion and sampling technique was used to estimate these three characteristics of progesterone metabolism in seven conscious and ten anaesthetized rats on day 16 of pregnancy. After steady state was achieved, four samples were collected during a 1-h period from each rat. Mean values for production rate and MCR of progesterone in conscious rats were 14·0 ±1·4 μmol/day and 63·2 ± 6·2 litres/day respectively. Both values were substantially reduced in anaesthetized rats (8.6 ±0·8 μmol/ day and 39·4± 3·4 litres/day respectively) and so blood concentration was unchanged. The production rate was positively related to the total mass of luteal tissue (common correlation coefficient, r = 0·61, P <0·05). There were no consistent changes in the three characteristics with time but variation within rats was high. The estimated coefficients of variation for production rate, MCR and blood concentration within rats were 26, 18 and 17% in conscious and 27, 20 and 23% in anaesthetized rats respectively. Short-term changes in production rate and MCR generally were in the same direction (P <0·05). This reduced variation in blood concentration which would otherwise have occurred if production rate and MCR were unrelated. The pregnant rat is clearly capable of rapid shifts in production rate, MCR and blood concentration of progesterone and the positive relationship between production rate and MCR has a homeostatic effect on blood concentration. J. Endocr. (1984) 102, 357–363


1999 ◽  
Vol 96 (4) ◽  
pp. 427-430 ◽  
Author(s):  
M. BLUM ◽  
Y. WEISMAN ◽  
S. TURGEMAN ◽  
S. CABILI ◽  
Y. WOLLMAN ◽  
...  

Normal pregnancy is associated with an increase in serum parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol). The effect of pregnancy on these hormones in chronic renal failure (CRF) is unknown. The present work was undertaken to study the changes of serum immunoreactive parathyroid hormone (iPTH) and calcitriol in pregnant rats with CRF. The following experimental groups were studied: CRF1 (5/6 nephrectomized virgin female rats), CRF2 (5/6 nephrectomized pregnant rats at day 20–21 of pregnancy), CRF3 (5/6 nephrectomized rats 2 weeks after delivery) and their respective sham-operated control groups: N1, N2 and N3. The 5/6 nephrectomy (CRF1) resulted in renal failure with very high serum iPTH (100±18 pg/ml) and low calcitriol levels (10.6±4.3 pg/ml) compared with normal rats [N1: 14±2.5 pg/ml (P< 0.001) and 18.2±4.2 pg/ml (P< 0.01) respectively]. The pregnancy in CRF rats (CRF2) resulted in normalization of serum iPTH levels (18.2±5.41 pg/ml), which was associated with a parallel increase in serum calcitriol (29.4±8.0 pg/ml) similar to that in pregnancy of normal rats (N2). Two weeks after delivery the CRF rats (CRF3) once again had high serum iPTH (87±17 pg/ml) and low calcitriol levels (9.3±1.2 pg/ml), similar to those observed in non-pregnant uraemic rats (CRF1). It is concluded that pregnancy decreases serum iPTH in 5/6 nephrectomized CRF rats most probably by the increased level of calcitriol synthesized by the feto-placental unit.


2018 ◽  
Vol 22 (4) ◽  
pp. 682-685
Author(s):  
E.N. Usychenko ◽  
Yu.I. Bazhora ◽  
E.M. Usychenko ◽  
V.A. Gudz

The data on the polymorphism of cytokine genes associated with individual reactivity on the effects of hepatitis C virus, predict the rate of progression of liver fibrosis. The purpose of this work is study the association of the polymorphic marker G308A of the TNFα gene with its quantitative content and degree of liver fibrosis in patients with chronic hepatitis C. A total of 100 patients with CSF were examined. The polymorphism of G308A gene’s TNFα was studied by amplification of the corresponding genome zones by PCR. The assessment of the degree of fibrosis was performed using the non-invasive Fibrotest method. The study of the quantity of TNFα cytokine in serum of patients was performed by ELISA. The distribution of genotypes on the investigated polymorphic loci was verified using Pearson's χ2 criterion. The frequencies of alleles and genotypes in the groups were compared using Pearson's χ2 criterion with Yates correction for continuity with the number of degrees of freedom 1. In order to detect the correlation dependencies between the individual parameters, the Spearman correlation coefficient was applied. It was found that a smaller degree of fibrosis was observed in carriers of the GG TNFα genotype, and a greater degree of fibrosis in the carriers of the genotype AA TNFα (moderate feedback between the degree of fibrosis and the genotypes of TNFα). The higher content of TNFα is noted in the carriers of the AA genotype TNFα, the lower content of TNFα - in the carriers of the GG TNFα genotype (moderate feedback between the TNFα genotypes and the TNFα content). It has been established that a higher TNFα content is observed in patients with F1-F0 fibrosis, a lower TNFα content in patients with F2-F3 fibrosis (a strong correlation between the degree of fibrosis and the amount of TNFα cytokine). It is assumed that the production of the cytokine is determined at the genetic level, and the severity of changes in the cytokine profile in chronic hepatitis C affects the course of the pathological process. An increase in the TNFα content in chronic hepatitis C may be a marker for significant morphological changes in the hepatic tissue and high activity of the inflammatory process.


1991 ◽  
Vol 10 (2) ◽  
pp. 269-278 ◽  
Author(s):  
R. P. Beliles ◽  
N. G. Makris ◽  
W. J. Scott

A compartmental pharmacokinetic-mathematical model for the time-dependent distribution of hydroxyurea (HU) in both the maternal plasma and embryonic fluids of pregnant rats and rhesus monkeys was developed. Across species scaling was based on maternal plasma clearance rates and compartmental sizes as a percent of the body weight of the dam. Mathematical optimization provided the compartmental transfer rates. The estimated maternal and embryonic concentrations of HU correlated well with the experimental pharmacokinetic data regarding both time and quantity for both the rat and the monkey. When the biological effective dose was considered to be the embryonic HU concentration over time (AUC), the dose to the individual embryos was higher in the monkeys (392 mg HU hr/L/day) than in the rats (69 mg HU hr/L/day) at an applied dose of 100 mg HU/kg administered to the dams. The AUC doses are consistent with the evaluation of the embryos of both species for teratogenic changes and embryonic death. The effect of repeated doses as compared with a single dose given only on one day of gestation was examined in the rat. Because of the rapid maternal clearance the carryover of embryonic HU concentration from one day to the next was minimal. A single treatment on Day 9 only was estimated to be sufficient to produce the adverse embryonic effects of HU on Days 9 through 12 as reported by Wilson et al. The sensitivity of the embryo to HU decreased with increasing embryonic age. The implications of the pharmacokinetic simulation and the temporal susceptibility for ongoing clinical trials of HU in the treatment of sickle cell anemia were reviewed. A human embryo dose of 69 mg HU hr/L/day was estimated to result from an i.v. dose of 10 mg/kg to the mother. This concentration produced no effect in the rat. An i.v. dose of 50 mg HU/mg was estimated to result in a human embryo dose of 353 mg HU hr/L/day which approaches a Rhesus monkey embryo dose that produced adverse effects in all embryos.


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